Sustainable Synthesis of Polynitroesters in the Freon Medium and their in Vitro Evaluation as Potential Nitric Oxide Donors

Abstract

A highly efficient, safe, and sustainable procedure was developed for the synthesis of various pharmacology-relevant and/or energy-rich nitroesters. It is based on nitration of corresponding alcohols with dinitrogen pentoxide in the liquid 1,1,1,2-tetrafluoroethane medium. The proposed approach is attractive for commercial applications because it offers significant advantages such as mild and clean reaction conditions, low operation pressure, available equipment, scalability, and facile fluid recycling. Structure−NO donor activity correlations were elucidated by an in vitro Griess assay for synthesized nitroesters and the obtained data may be useful for further in vivo experiments.

Facile and Efficient Nitration of 4‐Aryl‐1(2H)‐Phthalazinone Derivatives Using Different Catalysts

“…The goodness of using HNO 3 /P 2 O 5 as a nitrating mixture may be attributed to the potent dehydrating property of phosphorous pentoxide, which extracts water from nitric acid. When P 2 O 5 was mixed with fuming nitric acid 65 %, the N 2 O 5 [28,29] was formed, which is considered a potent nitrating agent that achieved the best result in this study.…”

“…[13,14] Moreover, nitro-aromatic compounds consider a key intermediate for the construction of a great variety of valuable products such as drugs, [15][16][17] dyes, [18] explosives and energetic materials. [19,20] Many methods for the nitration of aromatic compounds have been developed using different nitrating agents including HNO 3 , metal nitrates (Fe(NO 3 ) 3 , [21,22] Zr(NO 3 ) 4 , LiNO 3 , Mg(NO 3 ) 2 , Pb(NO 3 ) 2, Cr(NO 3 ) 3 , [23] sodium nitrites (NaNO 2 ), [24,25] KNO 2 , [26] NO 2 BF 4 [27] and N 2 O 5 [28,29] using different nitrating catalysts such as Lewis acids, [30] Bronsted acids (H 2 SO 4 , H 3 PO 4 , CH 3 COOH), ptoluene sulfuric acid (PTSA), [31] iodine(III)-catalyzed electrophilic nitration, [32] diaryliodonium salts, [33] Alumina sulfuric acid (ASA), [34] silica sulfuric acid, [35] dehydrating agents, [36] oxidizing agent catalysts (P 2 O 5 and Cerium Ammonium Nitrate (CAN)), [37] different organic solvents, [38] and may use solid support materials such as (silica contain zeolites), [39] and also some researchers studied nitration reactions under microwave [40] and ultrasound [41] irradiation. However, many problems have been observed, which result from introducing a nitro group into organic compounds particularly, over nitration, regioselectivity, [42] competitive oxidation and hydrolysis of sensitive compounds.…”

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors

“…However, GTN suffers from various side effects, such as headache, difficult or labored breathing, dizziness, and also may induce nitrate tolerance upon continuous exposure [ 24 ]. A similar pharmacological profile matches other organic nitrate-based pharmacologically active substances (e.g., isosorbide dinitrate) [ 25 ], although their levels of NO release are quite different [ 26 ]. Aside from organic nitrates, other nitrogen–oxygen acyclic species were reported as NO-donors: C - or N -nitroso compounds, nitrosothiols, oximes, hydroxylamines, hydroxyurea and metal-nitrosyl complexes (sodium nitroprusside) [ 22 ].…”

Nitration of aromatics with dinitrogen pentoxide in a liquefied 1,1,1,2-tetrafluoroethane medium

“…39 To increase the nitration efficacy for such cases, numerous Lewis and Bronsted acids were considered as heterogeneous catalysts, including zeolites, 43,44 bismuth and rare-earth metal triates, 45,46 iron(II) and zirconium(IV) acetyl acetates. 47,48 Recently, we have reported on N-and O-nitration reactions in the media of liqueed 1,1,1,2-tetrauoroethane (TFE), 36,49 an accessible and inexpensive refrigerant (R134a) widely used in different areas 50,51 from industrial and household units to medical inhalers, 52 where it is employed as gas-carrier due its complete nontoxicity. 53 This gaseous, at normal conditions, 54 resistant to strong oxidizers (including DNP) polar compound (DM ¼ 2.1 D) 54 can be easily turned to liquid under mild conditions.…”